{Reference Type}: Journal Article
{Title}: Discovery of Potent DAG-Lactone Derivatives as HIV Latency Reversing Agents.
{Author}: Ishii T;Kobayakawa T;Matsuda K;Nigorikawa K;Bolah P;Noborio A;Tsuji K;Ohashi N;Yoshimura K;Nomura W;Mitsuya H;Maeda K;Tamamura H;
{Journal}: ACS Infect Dis
{Volume}: 10
{Issue}: 6
{Year}: 2024 Jun 14
{Factor}: 5.578
{DOI}: 10.1021/acsinfecdis.4c00194
{Abstract}: Toward human immunodeficiency virus type-1 (HIV-1) cure, cells latently infected with HIV-1 must be eliminated from people living with HIV-1. We previously developed a protein kinase C (PKC) activator, diacylglycerol (DAG)-lactone derivative 3, with high HIV-1 latency-reversing activity, based on YSE028 (2) as a lead compound and found that the activity was correlated with binding affinity for PKC and stability against esterase-mediated hydrolysis. Here, we synthesized new DAG-lactone derivatives not only containing a tertiary ester group or an isoxazole surrogate but also several symmetric alkylidene moieties to improve HIV-1 latency reversing activity. Compound 9a, with a dimethyl group at the α-position of the ester group, exerted twice higher HIV-1 latency reversing activity than compound 3, and compound 26, with the isoxazole moiety, was significantly active. In addition, DAG-lactone derivatives with moderate hydrophobicity and potent biostability showed high biological activity.